Effect of aldosterone on the coupling between H+ transport and glucose oxidation.

Abstract

A B S T R A C T The mode of action of aldosterone on the energetics of H+ transport in the turtle bladder was examined with the rate of glucose oxidation as an index of the metabolic activity of the epithelium (we show that H+ transport is not coupled to fatty acid oxidation).Within 6 h of addition of aldosterone H+, transport increased; so did glucose oxidation. The amount of H+ transport per mole of 14CO2 produced from glucose oxidation was 15.6 eq mol-' in the control hemibladder, while in the aldosterone-treated bladder it was 13.6, A = 2.0+4.0 (n = 6). However, in bladders exposed to aldosterone for 20 h, the relation oftransport to glucose oxidation was significantly altered: control 10.8, aldosterone 16.4, A = 4.5+2.5, P < 0.02, ni = 7. The slope of H+ transport on the applied electrochemical gradient was steeper during both short-and long-term incubations. However, the maximum gradient necessary to nullify the net rate of secretion was unaltered in both experiments. Evidence is presented that aldosterone does not alter the passive backflux into the cell. In five additional experiments where aldosterone produced no significant stimulation of H+ transport, no change was noted in any of the metabolic or transport characteristics measured, suggesting that the alterations discussed above are dependent on the stimulation of H+ transport by the hormone.These results, along with some thermodynamic considerations, suggest that the effect of aldosterone is primarily exerted on the transport process rather than on metabolism. Further, it appears that prolonged stimulation of transport work leads to secondary alterations in the metabolic pathways reminiscent of the changes that occur in skeletal muscles of athletes undergoing physical conditioning.

Renal Vacuolar H+-ATPase

“…In addition, endocytosis of proteins such as albumin and immunoglobulin light chains into proximal tubule cells is inhibited by bafilomycin treatment (42, 343,344). Inhibition of vesicle acidification by other factors including NH 4 Cl and cadmium exposure also results in a reduction in endocytosis by proximal tubule epithelial cells both in vivo and in vitro (109,193,194,234). Vacuolar H ϩ -ATPase activity is also required for other important pathophysiological events, including viral infection.…”

“…This acid-base disturbance, which is often induced by the addition of NH 4 Cl to the drinking water (34, 101, 162, 276), induces a more pronounced expression of vacuolar H ϩ -ATPase subunits in the luminal membrane of type A intercalated cells in the late distal tubule, the connecting segment, and the collecting duct. This translocation of vacuolar H ϩ -ATPase into the membrane is paralleled by increased activity of NEM-, bafilomycin-or concanamycin-sensitive ATPase activity as well as proton extrusion (276).…”

Relationship between the Rate of H+ Transport and Pathways of Glucose Metabolism by Turtle Urinary Bladder

“…The function of the pentose shunt would be to produce reducing equivalents, NADPH, which are required for the biosynthesis of fatty acids. Although this possibility was not directly examined in the present study, we view it as unilikely because exogenous fatty acids fail to stimiiulate JH in substrate-depleted bladders and the metabolismii of fatty acids is not coupled to the rate of JH (27). Aniother explanationi is that the end product of the pentose phosphate shunt, NADPH, provides the source of protonis for translocationi across the luminal miiembrane.…”

Spironolactone. An aldosterone agonist in the stimulation of H+ secretion by turtle urinary bladder.

“…To overcome this limitation, three sets of separate comparisons were made between halves of bladders instead of the four-way comparisons in the quarters of bladders. First, exposure to aldosterone alone caused consistent stimulation of JH and JNa compared to control halves (14,17). Second, aldosteroneexposed halves were compared with and without pretreatment with spironolactone.…”